The GAPSID Study - How GLP-1 Analogues Prevent Steroid-Induced Diabetes

NCT06318442 | Recruiting

• 1 other identifier: 22HH8018
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

TITLE: How GLP-1 Analogues prevent steroid-induced diabetes (The GAPSID Study) DESIGN: A double-blind study evaluating how GLP-1 analogues, compared with metformin, prevent hyperglycaemia in response to a 7-day course of dexamethasone (DEX) 6 mg once daily. This is a mechanistic experimental medicine study. AIMS: To evaluate the mechanisms by which GLP-1 analogues reduce steroid-induced hyperglycaemia compared to metformin. OUTCOME MEASURES:

• Primary: Glucose tolerance in response to standardised mixed meal test (MMT) lasting for 240 minutes, measured in all participants at baseline and on day 7 DEX.
• Secondary: Indices of insulin resistance (M-value), beta-cell function (acute insulin response to glucose) and disposition, as measured by a combined IV glucose tolerance test and hyperinsulinaemic-euglycaemic clamp, performed at baseline and on day 7 DEX.
• Exploratory: Tissue specific changes in adipose AMPK determined from adipose and muscle biopsies, taken from a subset of approximately 8 individuals in each group. ELIGIBILITY: People living with pre-diabetes or lifestyle controlled diabetes STUDY DURATION: This study will take place over 3 weeks for each partcipant. Study procedures include 10 days of baseline continuous glucose monitoring (CGM) followed by 7 days of dexamethasone with GLP-1, metformin or placebo. Participants will attend a follow-up visit 3-5 days after completing the 7-day course of study drug. The study will run over a period of 3 years. ANTICIPATED IMPACT: Mechanistic evidence for the use of GLP-1 analogues, compared with metformin, in the treatment of steroid-induced diabetes.

Conditions

Steroid-Induced Diabetes; Steroid Induced Hyperglycemia

Outcome Measures

Primary Outcomes (1)

• Difference in Glucose tolerance

  Glucose tolerance as measured by glucose area under the curve (AUC), in response to standardised mixed meal test (MMT) lasting for 240 minutes. This will be measured in all participants at baseline and at the end of the study medication period (after 7 days of dexamethasone and study medication).

  Through study completion, on day 7 dexamethasone and study medication

Secondary Outcomes (4)

• Difference in insulin secretion

  Day 6 of dexamethasone and study medication

• Difference in insulin sensitivity

  Day 6

• Difference in insulin sensitivity

  Day 6

• Difference in insulin sensitivity

  Day 6

Other Outcomes (10)

• Mean glucose and glycaemic variation by continuous glucose monitoring (CGM), using a validated blinded system (Dexcom G7).

  Through study completion

• Changes in fasting gut hormones

  Through study completion, on day 7 dexamethasone and study medication

• Changes in fasting gut hormones

  Through study completion, on day 7 dexamethasone and study medication

Study Arms (3)

Once daily semaglutide

EXPERIMENTAL

Once daily semaglutide 3 mg (uptitrated to 3 mg twice daily after two days).

Drug: Semaglutide Oral Product

- Metformin

ACTIVE COMPARATOR

Metformin modified release tablets (500mg once daily for the first two days, then 500 mg twice daily).

Drug: Metformin Oral Tablet

Placebo

PLACEBO COMPARATOR

Placebo tablets

Drug: Placebo

Interventions

Semaglutide Oral Product DRUG

Oral semaglutide 3mg once uptitrated to twice daily

Once daily semaglutide

Metformin Oral Tablet DRUG

Metformin modified release tablets 500mg once daily uptitrated to twice daily).

- Metformin

Placebo DRUG

Placebo tablets

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥ 18 years;
• Male or female;
• Pre-diabetes (HbA1c ≥42 and \<47 mmol/mol, or lifestyle-controlled diabetes (HbA1c ≥48 and ≤52 mmol/mol); measurements within range on two separate occasions ≥90 days apart)
• Body mass index ≥22.5 kg/m2

You may not qualify if:

• Prior treatment with any diabetes medication within 90 days;
• Current or planned pregnancy, or current breastfeeding;
• Previous treatment with GC (topical, oral, injected) within 30 days or 90 days for extended-release injected GCs (e.g. Depo-Medrone);
• Continuing requirement for GC treatment (e.g. for steroid replacement, chronic inflammatory or immunological condition);
• Treatment with medications altering DEX pharmacokinetics (e.g. phenytoin, carbamazepine, ritonavir).
• History of pancreatitis, renal disease (eGFR \<30), severe hepatic impairment, gallbladder disorders, or GI disease (e.g. IBD), heart failure, history of medullary thyroid cancer (MTC), or previous skin reactions.
• History of giving blood or having taken part in another non-related study in the last three months
• History of any other medical, psychological condition, or use of any medications, which, in the opinion of the investigators, would either interfere with the study or compromise the safety of the participant.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College Healthcare NHS Trust

London, United Kingdom

RECRUITING

MeSH Terms

Interventions

Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Karim Meeran

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katharine Lazarus, MBChB, BSc

CONTACT

07555717544; k.lazarus@imperial.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2024
• First Posted: March 19, 2024
• Study Start: May 15, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: October 2, 2024

Record last verified: 2024-09

Locations

GB (1)